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York Biomedical Research Institute
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What causes neurodegeneration and how to combat it?

Neurodegenerative diseases, including dementias and motor neurone disease, affect nearly one million people in the UK and 57 million globally.

Interplay between genetics and environmental factors causes aberrant protein aggregation across different brain regions, such as amyloid plaques and tau tangles in Alzheimer's disease, α-Synuclein in Parkinson's disease, and TDP-43 in Amyotrophic Lateral Sclerosis (ALS). 

As these pathological protein aggregates signify and drive neurodegeneration, understanding the cause and impact of the proteinopathy is vital to combat neurodegenerative diseases.

Our lab investigates these pathogenic mechanisms using -omics, cell biology, and in vivo modeling. In particular, we study a disease-associated mutation that disrupts TDP-43's core function, leading to TDP-43 protein aggregation, cellular transcriptomic changes, abnormal cell response and eventually neuronal cell death. On the other hand, activating the cellular chaperone response is shown to reduce TDP-43 aggregation and rescue cell viability, leading to our ongoing drug development efforts to identify new chaperone activators.

 Publications

  • Ho A, Connor JP, Ahmed S, Droop AP, Chen HJ. Upregulation of Damage-Associated Molecular Patterns (DAMP) recognition pathways in Amyotrophic Lateral Sclerosis identified in the cross-study transcriptomic analysis. Under revision
  • Ho A, Chen HJ (2026) Targeting the activation of heat shock proteins as the potential treatment of neurodegenerative diseases. Expert Opin Ther Targets 30 (1): 5-7
  • Magarotto M, Chen HJ (2026) Crossroad of Motor Neuron Disease and Dementia: Insights from TDP-43 RNA-Binding Deficiency. Neural Regen Res 21(10):4900-4901
  • Magarotto M, Gawne RT, Vilkaite G,Beltrami M, Mason AS, Chen HJ (2025) Familial ALS/FTD-associated RNA-Binding deficient TDP-43 mutants cause neuronal and synaptic dysregulation in vitro. Hum Mol Genet 34(17):1480-1494
  • Ho A, Jeganathan F, Bictash M, Chen HJ (2025) Identification of novel small molecule chaperone activators for neurodegenerative disease treatment. Biomedicine & Pharmacotherapy 187:118049 

Lead researcher